The objective of the proposed research is to develop an immunologically specific adsorbent for use in extracorporeal systems to remove immunoreactive IgM from the serum of patients for primary biliary cirrhosis (PBC). By standard immunologic techniques, antibodies to human IgM will be isolated. These antibodies will be covalently linked to silica to produce a specific immunoadsorbent. This adsorbent will be tested in vitro in a Phase I study to assess the quantitative removal of IgM and immunoroeactive IgM from normal and pathologic sera, respectively. If efficatious, then IgM will be isolated from normal human serum and monoclonal antibodies to this IgM will be produced. The monoclonal antibody will be covalently linked to silica, and tested in vitro as described above. Upon the in vitro demonstration of quantitative and specific removal of immunoreactive IgM from the pathologic sera, immunoadsorbent columns (housed in disposable cartridges) will be developed for use in a Phase Ii in vivo study which will assess the effect of such treatments when applied to patients with PBC. This in vivo study (Phase II) will provide evidence for the efficacy of this approach in removing immunoreactive IgM. Present evidence suggests that the IgM from PBC patients may behave like an immune complex, although it has the same physical-chemical properties as normal IgM. When feasible, a long term study will allow assessment of whether this specific immunoadsorbent extracorporeal technique will alter the natural history of the disease. Currently there is no specific treatment for PBC, and its natural course, although variable, tends to be progressive, leading to death in ten to fifteen years. From this proposed research plan, it is anticipated that a biologically specific extracorporeal immunoadsorbent will be developed which will allow periodic removal of immunoreactive IgM from patients sera resulting in improvement of their altered immune state. In addition, it is anticipated that this specific extracorporeal approach will become commercially available, and may be extended to other "autoimmune" disorders where altered immune mechanisms are presumed to play a role in pathogenesis.